The specific aims of the proposed research are to investigate the nature of the age-related susceptibility of the newborn and developing human infant to infection with clinically relevant bacterial pathogens. This will be accomplished by examination of several parameters of phagocytic cell functioning the normal infant as well as the infant with clinically documented bacterial infection. This project is based upon the hypothesis that due to maturational deficiencies in phagocytic function, the neonatal and young infant is at increased risk to certain severe bacterial infections. Parallel investigations will also be conducted in the ongoing experimental rat model system in which maturational changes in the immune response to challenge infection can be systematically and rigorously examined, and compared with those of the human. The research project will be conducted by a multidisciplinary team of basic and clinical scientists who will pursue the research objectives around a central unifying theme of immaturity of the human infant's system. We anticipate that through the combined approach of human studies as well as the animal model system, it should be possible to delineate not only defective cellular responses of the developing infant important in diagnosis and treatment, but also it should be possible to provide suitable predictive markers for the identification of human infants at risk to serious bacterial infections.